Marchetti A, Robbins J, Campbell G, Buttitta F, Squartini F, Bistocchi M, Callahan R
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Virol. 1991 Aug;65(8):4550-4. doi: 10.1128/JVI.65.8.4550-4554.1991.
The frequency with which int-1 and int-2 are rearranged in mouse mammary tumors by mouse mammary tumor virus (MMTV)-induced insertional mutagenesis is a consequence of the host genetic background. In 75% of C3H mammary tumors, int-1 is rearranged by MMTV insertion, whereas only 30% of BALB/cfC3H tumors contain a virus-induced rearrangement of int-1. This difference is significant (P less than 0.005) and could not be accounted for by the potentially additive effect of the genetically transmitted Mtv-1-encoded virus in C3H mice. Similarly, MMTV-induced rearrangement of the int-2 gene in mammary tumors of the R111 mouse strain (59%) occurred at a significantly (P less than 0.025) higher frequency than in BALB/cfR111 (25%) mammary tumors. Moreover, in BALB/cfR111 mammary tumors, there is evidence that rearrangement of int-1 and int-2 does not occur independently (P less than 0.025). These results suggest that the long history of inbreeding for high tumor incidence of C3H and R111 mouse strains has selected for the fixation of host mutations which either complement the action of the particular int gene or affect the sensitivity of specific subpopulations of mammary epithelium to infection by particular strains of MMTV.
通过小鼠乳腺肿瘤病毒（MMTV）诱导的插入诱变，int-1和int-2在小鼠乳腺肿瘤中发生重排的频率是宿主遗传背景的结果。在75%的C3H乳腺肿瘤中，int-1因MMTV插入而发生重排，而只有30%的BALB/cfC3H肿瘤含有病毒诱导的int-1重排。这种差异具有显著性（P小于0.005），并且不能用C3H小鼠中遗传传递的Mtv-1编码病毒的潜在累加效应来解释。同样，MMTV诱导R111小鼠品系乳腺肿瘤中int-2基因的重排（59%）发生频率显著高于BALB/cfR111（25%）乳腺肿瘤（P小于0.025）。此外，在BALB/cfR111乳腺肿瘤中，有证据表明int-1和int-2的重排并非独立发生（P小于0.025）。这些结果表明，C3H和R111小鼠品系因高肿瘤发生率而进行的长期近亲繁殖，已经选择固定了宿主突变，这些突变要么补充特定int基因的作用，要么影响乳腺上皮特定亚群对特定MMTV毒株感染的敏感性。
